First Genetic Test Hits Market to Show Which AIDS Drugs Will Fail in Each Patient

Food and Drug Administration (FDA) officials announced their approval of the first gene-based test to tell quickly whether an HIV patient's virus is mutating, thereby making a particular drug therapy fail. The FDA described Visible Genetics Inc.'s Trugene, one of the most complex genetic test systems to clear the FDA, as an important tool in helping doctors select the most effective medication to fight each patient's HIV.

HIV naturally grows resistant to medications over time. Experts estimate that 60 percent of patients have a virus that is resistant to at least one drug. However, until now, the only way to discover which drugs a patient's HIV disease is resistant to was for the patient to undergo tests to monitor the amount of virus in the bloodstream. An increase in the viral load can mean that HIV is growing resistant to one or more drugs. To check a patient's blood for genetic mutations that affect one of the 15 AIDS drugs requires additional laboratory testing not routinely available.

With Trugene, a sample of blood is sent to one of 130 laboratories where Visible Genetics has trained personnel. Specially designed computer programs decode the HIV genes, identify all genetic mutations and match the mutations to a list of more than 70 mutations currently known and linked to resistance to specific AIDS drugs. The test takes three days to complete and will cost $300-$500 per patient.

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"It's a major step forward in HIV treatment," said R. Scott Hitt, president of the American Academy of HIV Medicine. But "it is only one piece of the puzzle" in choosing the right medicine, he cautioned, urging patients to seek treatment from HIV specialists who can properly interpret the test results.

Trugene is 98 percent accurate, said FDA medical reviewer Dr. Andrew Dayton. More importantly, as scientists discover additional mutations -- a very rapidly changing field -- the new data can be added to the computer software so that the test remains accurate in everyday practice, he said.

FDA researchers tested the gene sequencer in an agency lab and approved the sale of Trugene late Wednesday after a year of review. This is record review time for such a complex new science, Visible Genetics president Richard Daly said. The test became available on Thursday. (Associated Press, 09.27.01, Lauran Neergaard)

Study: HIV Patients With Case Managers Have Fewer Unmet Needs

HIV-infected adults with case managers who help coordinate their health care had fewer unmet needs and higher use of HIV medications, according to a study in today's issue of Annals of Internal Medicine (October 16, 2001; 135 (8): 557-565). The study reported on 2,437 HIV-infected adults who visited inpatient and outpatient medical facilities in 52 urban and rural areas in 1996 and 1997. After looking at the patients at the start of the study and again six months later, researchers found that nearly 66 percent of those without case managers had needs that were not met -- nearly 10 percentage points higher than the level of unmet needs for patients who had case managers.

Patients with case managers were more likely to get income assistance, health insurance, emotional counseling, substance abuse treatment and other care. They also were more likely to get medicines like drug combination therapy and protease inhibitors, a factor that the study's lead author Dr. Mitchell H. Katz said he found "startling." The study noted that an increasing number of people with HIV are living in poverty and need both support services and medical care, making the role of case managers particularly important for doctors and patients. Still, the study noted that just 56 percent of HIV patients had case managers and that more funding is needed to get assistance -- and medications -- to where they're needed.

"Unless funds increase, we'll have to put new clients on a waiting list or discharge existing clients," said Kevin R. Conare, executive director of Action AIDS, Philadelphia's largest provider of HIV case management services. In a related editorial, also in today's Annals, Conare and Dr. William C. Holmes of the University of Pennsylvania School of Medicine said that case management services for HIV-infected people are at risk if federal funding is not increased. Most money now comes from the federal Ryan White Comprehensive AIDS Resources Emergency (CARE) Act. The Bush administration's fiscal 2002 budget froze the program's funding at $1.8 billion -- the same amount as 2001. Holmes said the program needs $300 million more. (Associated Press, 10.16.01, Joann Loviglio)

Experts Fear a Risky Recipe: Viagra, Drugs and HIV

Like many straight men, many gay men are using Viagra as a remedy for erectile dysfunction. But surveys disclose that many gay Viagra users are taking it along with ecstasy and other illegal drugs, leading some HIV educators to fear a rise in unprotected anal intercourse. And, when combined with the nitrite-based "poppers" some gay men inhale to heighten sensations during sex, Viagra can cause dizziness, strokes or heart attacks.

In a recent survey of men visiting a San Francisco STD clinic, 32 percent of gay respondents had used Viagra in the past year, compared to just 7 percent of straight men. The gay men who used Viagra reported having had more recent sexual partners than the gay men who did not use it, and they were more likely to have an STD currently. Thirty percent of gay HIV-negative Viagra users reported having had unprotected anal sex with HIV-positive men or with men of unknown HIV status, compared to just 15 percent of gay HIV-negative men not using Viagra. More than half the gay men had obtained Viagra from a friend instead of a doctor.

Dr. Jeffrey Klausner, director of STD prevention at the San Francisco Health Department, said that some gay men use Viagra to counteract the effects of speed, which can cause erection difficulties. "Viagra can turn people with chemically induced erectile dysfunction into more effective transmitters of HIV and other STDs," he said.

Still, it is unclear whether Viagra use leads to risky behavior or whether those who engage in risky sex are more likely to use Viagra. And some Viagra advocates suggest that it may actually reduce HIV transmission by making it easier to maintain an erection while wearing a condom.

Klausner said he hoped the San Francisco survey's results would help persuade Viagra-maker Pfizer to create educational campaigns about the drug's use and abuse. A Pfizer spokesperson said he did not know whether the company would pursue a gay-oriented ad campaign. "Our position to not use Viagra for recreational purposes is well-known, but any pharmaceutical product can be abused," he said. (New York Times, 10.16.01, David Tuller)

AIDS Patients Do OK With Transplants

According to researchers at the World Congress of Nephrology in San Francisco, patients infected with HIV appear to do well following the receipt of donor kidneys and livers. Despite the fact that patients routinely must receive cyclosporine, an immuno-suppressant administered so that organ rejection does not occur, HIV/AIDS patients do gain from the operation. "Frankly, a lot of us thought that giving cyclosporine to these patients would be almost immediately fatal," said Dr. Lynda Frassetto, associate clinical professor of medicine at the University of California-San Francisco.

Frassetto said that eight of her first nine transplant patients have survived the procedure, one for as long as 18 months. The patient who died, Frassetto told UPI, was infected through blood products used to treat childhood leukemia. He received two liver transplants but died 15 months later of advanced hepatitis. Three patients received livers. Six patients received kidneys. With the exception of one teenager, adults who received organs ranged in age from 38 to 53 at the time of the operation.

In a presentation at the conference, co-sponsored by the American Society of Nephrology and the Amsterdam-based International Society of Nephrology, Frassetto discussed the details of the study. Nine patients who had HIV and stable viral loads thanks to antiretroviral drugs were selected. They were all treated for any other existing disease or condition before undergoing transplant. They received a transplant because they were either next in line on a transplant list, had a family member donor, or agreed to accept organs that were rejected from other institutions, usually because the donor was elderly.

In the patients receiving cyclosporine, the level of CD4-positive cells increased, sometimes markedly. The larger the number of CD4-positive cells, the greater the immune competence. "Fifteen years ago, having HIV infection was an absolute exclusion for receiving a transplant," said Dr. Solomon Smith, a nephrologist and AIDS specialist affiliated with the Veterans Affairs Hospital in Columbia, S.C. "But now, with treatments, we have extended the life expectancy of AIDS patients so that these patients with liver and kidney failure can benefit from these transplants."

Frassetto said that the procedures are still new and are not to be routinely advocated. "Any transplant into an HIV-infected patient should be done as part of an experimental protocol," she said. "This is still a very complicated procedure and requires the help of a lot of specialists in surgery, transplantation, AIDS treatment as well as nephrology."

AIDS During Wartime

"...The deluge of dollars from public and private sources has been astonishing in the aftermath of the [Sept. 11] attacks. In two weeks, charities raised half a billion dollars for victims and their families. The US government is said to have committed $40 billion to the disaster. The entertainment industry presented a telethon shown on four major television networks (and several cable channels) that raised over $150 million in just two hours.

"The phenomenal reaction to the attacks will most certainly have unfavorable consequences to all national programs including efforts to combat AIDS that were underway or being planned before Sept. 11... There is great concern about the future of AIDS and how the government and public will respond in wartime....

"Government HIV research efforts will most certainly be affected as the National Institutes of Health begins prioritizing funds for research into the threat of biological warfare.

"Why didn't the world react to the global AIDS epidemic as effectively as it has to the terrorist attacks? One wonders, given the huge loss of life caused by AIDS, and the fact that the global crisis remains an overwhelming menace, why hasn't more been done? While it is not fair to pit disasters against each other, just as it is not fair to claim any disease is more exceptional than another, it is shocking to compare the worldwide and national response to AIDS to the response to the terrorist attacks. Some will say that the attacks were more immediate and emotional, but anyone who has survived AIDS would say that AIDS is just as poignant and still spreading out of control....

"[According to long-time San Francisco AIDS activist Laura Thomas], 'We need to develop strategies to keep a focus on AIDS that doesn't detract from the need to take care of the survivors of the recent attacks. Pouring more money into defense and into limited civil rights in this country will only hinder our ability to care for people here, including people living with HIV/AIDS.'..." (Bay Area Reporter (San Francisco), 10.04.01, Matt Sharp)

HIV Highly Contagious Before Symptoms Show

HIV may be highly transmissible before an infected person experiences its first, flu-like symptoms, and before HIV tests can detect the virus, researchers reported last week. The findings underscore the importance of consistent safe sex in preventing AIDS. The investigators studied five couples in whom HIV transmission occurred soon after one partner contracted the virus -- and as early as one week before the partner developed the flu-like symptoms that characterize early HIV infection.

"The main thing that's new is that we've shown for the first time that sexual transmission can happen readily and very soon after exposure," said a statement from Dr. Christopher D. Pilcher of the University of North Carolina-Chapel Hill. Researchers had suspected but not documented this phenomenon, according to Pilcher. He and his colleagues reported their findings in the Oct. 10 issue of the Journal of the American Medical Association (2001; 286: 1713).

During the period shortly after transmission, known as primary HIV infection, virus levels soar in the blood, and short-lived symptoms such as fever, fatigue and swollen glands may occur. But because the immune system has not yet produced antibodies to the infection, standard tests for HIV antibodies cannot detect the infection. Researchers have theorized that during this period, large amounts of the virus are "shed" into the genital tract and make the patient highly infectious. The current study suggests that this is, indeed, the case.

The team came to its conclusions by taking the couples' sexual histories and genetically analyzing the HIV in their blood samples. All transmission had been suspected of occurring when one partner had a documented primary HIV infection. The researchers concluded that each case of a documented primary infection presents "a unique public health opportunity" to track down that person's recent sexual contacts and prevent the further spread of HIV.

"If you engage in unsafe sex, you cannot assume that you are not infected or infectious because you had a negative antibody test for HIV. The most commonly used tests can't show HIV for several weeks," Pilcher said. (Reuters Health, 10.18.01)

Cases of HIV Among Inmates in Indiana Prisons Are Leveling Off

The occurrence of HIV among inmates in Indiana prisons has leveled off, though it still remains about 10 times higher than the known incidence of HIV in the state's overall population.

There are an estimated 215 people in Indiana prisons this year with HIV. Department of Correction officials said that roughly 1 percent, or 21,507 people, in Indiana prisons are HIV-positive.

The percentage of HIV-positive inmates in Indiana is well below the national average of 2.1 percent. A Bureau of Justice Statistics report issued in July showed that while the number of HIV cases in US prisons has increased, the number of HIV-positive prisoners has grown at a slower rate than the overall prison population. Prison and health experts attribute the trend to increased awareness of the disease and improved treatment.

"Overall the last 10 years we've gone from not knowing, not caring, to people knowing a lot about HIV and people actually caring about the kind of care they provide," said Anne DeGroot, editor of Brown University's HIV and Hepatitis Education Prison Project. "There's been sort of an awakening of physicians in the facilities, and that's what's making the change." Still, health experts and advocates for AIDS patients express concern about maintaining the safety of prisoners living with the disease and preparing them for release to society. They believe more awareness and education are needed.

HIV-positive inmates receive medical treatment at Indiana prisons through the Prison Health Services, the private company under contract with the state to provide health care for all inmates. HIV-positive inmates are also counseled upon entering and leaving any state prison. Upon intake, inmates receive information on ways to avoid the spread of HIV and other infectious diseases such as hepatitis and TB. Caseworkers at the Damien Center, an Indianapolis AIDS service organization, said the Department of Correction doesn't have enough staff to provide the needed pre-release counseling. For many inmates, living with HIV or AIDS after their release isn't a big priority. "They're more concerned about, 'Where am I going to sleep? Where am I going to eat?'" said Damien caseworker Sheryl Phillips. (Associated Press, 10.21.01)

In view of the adverse affects that accompany antiretroviral therapy, precise data on effects have long been indicated. Background data on adverse events to antiretroviral treatment have been recorded in clinical trials, post-marketing analyses, and in anecdotal reports. But no systematic study has been done to assess adverse events.

Using a standard clinical and laboratory method, the investigators evaluated the prevalence of adverse events in 1,160 patients who were receiving antiretroviral treatment. They measured the toxic effects associated with various regimens: protease inhibitor (PI), non-nucleoside and nucleoside analogue reverse transcriptase inhibitor and specific compounds. Data were obtained from outpatients in the Swiss HIV Cohort Study using a structured interview and laboratory analyses to identify and describe all potential adverse events attributed to treatment according to standard definitions. Identification of independent associations using logistic regression analysis was also utilized.

The Swiss HIV Cohort Study is a prospective cohort study of individuals with HIV-1 who were followed up in one of seven Swiss clinics. Patients were identified by the type of antiretroviral regimen they were on. Patients who had changed their regimen in the last 30 days were excluded from the study. During the visit, physicians completed a questionnaire based on classification used by the AIDS Clinical Trials group on adverse events. According to the authors, "Physicians explicitly asked patients if symptoms listed in the questionnaire had arisen within the 30 days preceding the visit. Lipodystrophy was described according to Carr and colleagues. Potential adverse events were scored according to severity (1=mild, 2=moderate, 3=severe, 4=serious) and the likelihood of resulting from antiretroviral treatment (unlikely, possible, probable, and certain), after the definition of the World Health Organization." Standard comprehensive laboratory assays were done on each patient on or immediately before (<10) their clinic visit.

The results of the study indicated that 47 percent of patients had clinical adverse affects from antiretroviral combination therapy. Nine percent of effects were graded as serious or severe. Twenty-seven percent of laboratory results showed adverse effects, and 16 percent of these were rated serious or severe. The more drugs taken in combination, the lower the HIV levels but the higher the likelihood of side effects.

According to the investigators, "It should be underscored that more than two-thirds of patients might have complaints if precisely questioned and that adverse events have an effect on adherence and on development of viral resistance, which might lead to treatment discontinuation or failure. Yearly surveys using the proposed cross-sectional analysis could help to assess changes in prevalence of specific toxic effects and in overall well-being of patients receiving antiretroviral treatment." The authors, in addition, recommended that post-marketing surveillance of toxic effects be conducted by pharmaceutical companies. (Lancet, 10.20.01, Vol 358; No 9290: P 1322-1327, Jacques Fellay et al.)

Study Shows Gay Men in San Francisco Less Afraid of HIV

According to a just-released University of California-San Francisco (UCSF) study, gay men don't find HIV as threatening as they once did; ads for AIDS drugs are seen as glamorizing life with HIV; and there is increased acceptance of unprotected sex.

Recent San Francisco Department of Health projections indicate a rising rate of new HIV infections, translating into about 750 new infections this year. Author Stephen Morin, director of the UCSF AIDS Policy Research Center, said the study's aims were to get gay men to explain the increase and to define prevention messages that might reduce risk among gay and bisexual men.

"The community norm has changed. Guys in the survey told us a friend may go on a date, or to a bathhouse, but the question, 'Were you safe?' doesn't come up. That 'Friends don't let friends drive drunk' kind of social support that came out loud and clear -- there's been a real deterioration in that. And it seems to be a major way people felt supported for staying negative," Morin said.

The study was conducted last summer with 55 gay and bisexual San Francisco men, who were divided into six focus groups. The men recommended a new social marketing campaign with ads on television and in bus shelters, magazines, bars and sex clubs to encourage men to dispel HIV myths by talking with their friends.

"Friends Can Be Good Medicine -- Talk About HIV" was one suggested slogan. Surveyed men also expressed concern that ads for AIDS medications glamorize life after infection, and these need to be balanced with images of men suffering the drugs' side effects. New ads are set to be ready by early next year, but Survive AIDS member Jeff Getty said a better tactic would be to send gay men to sex clubs as safe sex advisers. (San Francisco Chronicle, 10.22.01, C. Heredia)

HIV Infection May Trigger Neurologic Disorder

A disorder similar to amyotrophic lateral sclerosis (ALS) has been associated with HIV-1 infection, prompting the suggestion that viral infection might precipitate the disorder in some people. In a retrospective study of 1,700 patients with HIV infection and neurological symptoms seen between 1987 and 2000, Dr. Antoine Moulignier of the Foundation Adolphe de Rothschild in Paris and his colleagues identified six patients who met international criteria for definite, probable or possible ALS. The incidence of the disorder was 3.5 per 1,000, well above the expected incidence in the general population of 0.4 to 1.76 per 100,000 (Neurology 57 [6]:995-1001, 2001).

The ALS-like syndrome was the first manifestation of HIV-1 in all of the patients. Presenting symptoms included tongue fasciculations and distal motor weakness in one or more limbs and initially were reminiscent of those of monomelic amyotrophy. However, the rapid progression of symptoms and the young age of the patients indicated that the disorder was a variant of ALS, rather than the classic disease.

In an accompanying case report, Dr. D.J.L. MacGowan and associates at Beth Israel Medical Center in New York described a 32-year old woman who presented with a rapidly progressing ALS-like syndrome and was found to be HIV-positive (Neurology 57 [6]:1094-97, 2001). Multidrug cocktails and improved control of HIV-1 viral load have made the disorder less common, Moulignier and his associates said. All seven patients improved or stabilized transiently following treatment with zidovudine, another nucleoside analogue, or active antiretroviral therapy. In an editorial, Dr. Burk Jubelt and Dr. Joseph R. Berger said that viral causes should be considered in patients presenting with the classic clinical signs of ALS "because HIV-ALS syndromes are treatable" (Neurology 57 [6]:945-46, 2001). (Internal Medicine News, 10.15.01, Vol 44; No 39: P 28, Norra Macready)

In Caribbean, People With HIV Say Discrimination Tops List of Concerns

When Elmar Wishart became seriously ill from HIV complications, he said doctors in the South American country of Guyana refused to treat him. "Facilities there are inhuman," said the 45-year-old Guyana native, who was diagnosed with the virus in 1990. Wishart and others at this week's 10th International Conference for People Living with HIV/AIDS in Trinidad say one of the remaining obstacles in the battle against AIDS is the stigma attached to the disease.

An estimated 2 percent of people in the Caribbean, excluding Cuba, have HIV/AIDS -- the world's highest regional infection rate after sub-Saharan Africa. In Cuba, extensive treatment and prevention have kept infection rates extremely low. But elsewhere in the Caribbean, discrimination has prevented some from getting treatment. In socially conservative Jamaica, for example, 66 percent of AIDS cases are diagnosed just before or after death, according to Jamaica's National HIV/AIDS control program. "People are brought up to think those with HIV are immoral," said Jamaican Dorothy Blake, spokesperson for the Caribbean Regional Network of People Living with HIV/AIDS.

Out of 150 HIV-positive Trinidadians attending the conference, none have publicly disclosed their status, said Claudette Francis, coordinator with Community Action Resource, Trinidad's AIDS counseling center. "Stigma is one of the greatest impediments in fighting HIV and AIDS," said Frenk Guni of Zimbabwe, a member of the Global Network for People Living with HIV/AIDS, who has been HIV-positive for 14 years. "When I first came out in the open about my HIV status, my relatives cut relations with me. I was gripped with fear of being abandoned," said Guni. Like Wishart, Guni said many people living with the virus around the world are denied medical treatment. In the Caribbean, about 500,000 people are living with HIV, according to the Caribbean Task Force on HIV/AIDS. (Associated Press, 10.30.01, Angela Potter)

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